Placebo Rates in Inflammatory Bowel Disease: An Individual Patient Data Meta-analysis of Randomized Controlled Trials

Inflammatory bowel disease (IBD) is a condition that causes swelling and pain in the digestive tract, which is the tube that carries food from the mouth to the stomach and subsequently to the anus. IBD is a common disease and 6.8 million people around the world suffer from it – and that number is growing (Global Burden of Disease Inflammatory Bowel Disease Collaborators, 2020). While there is no cure for IBD, there are several therapies available to treat the disease and more that are in development.

To learn whether a new therapy works to treat IBD, it must be tested in research studies. One way to do this is to compare the therapy to a placebo, which is a “fake” copy of the real therapy. The placebo looks like the real therapy, but it contains none of the medicine. In such a study, some IBD patients will be given therapy while others will be given placebo. Usually this is decided randomly (like the flip of a coin) and neither the patients nor their doctors know what they are taking until the study is over. If a therapy works, the group treated with the real therapy should do better than the group that received the placebo. Sometimes a therapy works very well and there is a big difference between the groups; other times the therapy has a small effect, or none at all, and the difference between the groups is lessened or disappears. But seeing the real benefit of a new therapy is made harder by something called the “placebo effect.” The placebo effect is a benefit that a person feels because of their belief in a therapy even though the improvement is not due to the therapy itself. For example, in a study where participants do not know if they are receiving therapy or placebo, it is common for those in the placebo group to still report some improvement in symptoms despite not receiving any medicine (Elsenbruch et al., 2015). There are many possible reasons for the placebo effect and previous research has identified several study-specific factors that contribute (Jairath et al., 2017; Jairath et al., 2020; Duijvestein et al., 2020). However, more research is needed.

In this study, we want to take a close look at both study factors and independent study participant characteristics that are linked to the placebo effect. By identifying these factors, this study aims to estimate placebo response in IBD studies and improve the design of future studies in IBD by reducing the impact of the placebo effect and making it easier to estimate the real benefit of any new therapies.